Linked Life Data

20647008

Source:http://linkedlifedata.com/resource/pubmed/id/20647008

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-8-24
pubmed:abstractText
Although internal ribosome entry site (IRES)-mediated translation is considered important for proper cellular function, its precise biological role is not fully understood. Runx1 gene, which encodes a transcription factor implicated in hematopoiesis, angiogenesis, and leukemogenesis, contains IRES sequences in the 5' untranslated region. To clarify the roles of the IRES element in Runx1 function, we generated knock-in mice for either wild-type Runx1 or Runx1/Evi1, a Runx1 fusion protein identified in human leukemia. In both cases, native promoter-dependent transcription was retained, whereas IRES-mediated translation was eliminated. Interestingly, homozygotes expressing wild-type Runx1 deleted for the IRES element (Runx1(Delta IRES/Delta IRES)) died in utero with prominent dilatation of peripheral blood vessels due to impaired pericyte development. In addition, hematopoietic cells in the Runx1(Delta IRES/Delta IRES) fetal liver were significantly decreased, and exhibited an altered differentiation pattern, a reduced proliferative activity, and an impaired reconstitution ability. On the other hand, heterozygotes expressing Runx1/Evi1 deleted for the IRES element (Runx1(+/RE Delta IRES)) were born normally and did not show any hematological abnormalities, in contrast that conventional Runx1/Evi1 heterozygotes die in utero with central nervous system hemorrhage and Runx1/Evi1 chimeric mice develop acute leukemia. The findings reported here demonstrate the essential roles of the IRES element in Runx1 function under physiological and pathological conditions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1095-564X
pubmed:author
pubmed:copyrightInfo
(c) 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
345
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
226-36
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
A 5' untranslated region containing the IRES element in the Runx1 gene is required for angiogenesis, hematopoiesis and leukemogenesis in a knock-in mouse model.
pubmed:affiliation
Department of Molecular Oncology, Research Institute of Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't